2014 Fiscal Year Final Research Report
Elucidation of molecular mechanism of stress-induced cardiomyopathy through brain-heart interaction.
| Project/Area Number |
25670395
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Takahide 慶應義塾大学, 医学部, 講師(非常勤) (00383894)
KANAZAWA Hideaki 慶應義塾大学, 医学部, 特任講師 (40338033)
SUKEGAWA Hiroaki 慶應義塾大学, 医学部, 助教 (60535607)
TABEI Ryota 慶應義塾大学, 医学部, 助教 (20573322)
MUNAKATA Masahito 慶應義塾大学, 医学部, 共同研究員 (40445284)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | ストレス / 脳 / サイトカイン / 脳心連関 / 炎症 / 臓器連関 |
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| Outline of Final Research Achievements |
Major emotional stress may induce stress cardiomyopathy (SC), although the precise molecular mechanisms remain unclear. Using an animal model of SC, we first located the central cardiac sympathetic nerves (CSNs) in the hypothalamus innervating the left ventricular (LV) apex, and then investigated the gene expression changes in these regions. We found that chemokine ligand 2 (Ccl2), produced by activated astrocytes, strongly stimulated the central CSNs. The subsequent sympathetic activation upregulated neuropeptide Y (NPY) expression in both the stellate ganglion (SG) and CSNs. NPY in turn had a negative inotropic effect and strongly blocked -adrenergic stimulation. Thus, administration of Ccl2 into the central neurons evoked SC and increased NPY at the SG. Moreover, siRNA downregulation of NPY in the SG completely abrogated the induced SC. Overall, our results provide to explain how emotional stress affects molecular signals in the brain, leading to LV apical ballooning.
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| Free Research Field |
医歯薬学
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